Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors

Ligaya M. Simpkins, Scott Bolton, Zulan Pi, James C. Sutton, Chet Kwon, Guohua Zhao, David R. Magnin, David J. Augeri, Timur Gungor, David Rotella, Zhong Sun, Yajun Liu, William S. Slusarchyk, Jovita Marcinkeviciene, James G. Robertson, Aiying Wang, Jeffrey A. Robl, Karnail S. Atwal, Robert L. Zahler, Rex A. Parker & 2 others Mark S. Kirby, Lawrence G. Hamann

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with β-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold.

Original languageEnglish
Pages (from-to)6476-6480
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number23
DOIs
StatePublished - 1 Dec 2007

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Dipeptidyl-Peptidase IV Inhibitors
Structure-Activity Relationship
Scaffolds
Nitrogen
Amino Acids

Keywords

  • DPP4
  • Diabetes
  • GLP-1
  • Non-nitrile
  • Serine protease

Cite this

Simpkins, L. M., Bolton, S., Pi, Z., Sutton, J. C., Kwon, C., Zhao, G., ... Hamann, L. G. (2007). Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors. Bioorganic and Medicinal Chemistry Letters, 17(23), 6476-6480. https://doi.org/10.1016/j.bmcl.2007.09.090
Simpkins, Ligaya M. ; Bolton, Scott ; Pi, Zulan ; Sutton, James C. ; Kwon, Chet ; Zhao, Guohua ; Magnin, David R. ; Augeri, David J. ; Gungor, Timur ; Rotella, David ; Sun, Zhong ; Liu, Yajun ; Slusarchyk, William S. ; Marcinkeviciene, Jovita ; Robertson, James G. ; Wang, Aiying ; Robl, Jeffrey A. ; Atwal, Karnail S. ; Zahler, Robert L. ; Parker, Rex A. ; Kirby, Mark S. ; Hamann, Lawrence G. / Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 23. pp. 6476-6480.
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abstract = "The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with β-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold.",
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Simpkins, LM, Bolton, S, Pi, Z, Sutton, JC, Kwon, C, Zhao, G, Magnin, DR, Augeri, DJ, Gungor, T, Rotella, D, Sun, Z, Liu, Y, Slusarchyk, WS, Marcinkeviciene, J, Robertson, JG, Wang, A, Robl, JA, Atwal, KS, Zahler, RL, Parker, RA, Kirby, MS & Hamann, LG 2007, 'Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 23, pp. 6476-6480. https://doi.org/10.1016/j.bmcl.2007.09.090

Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors. / Simpkins, Ligaya M.; Bolton, Scott; Pi, Zulan; Sutton, James C.; Kwon, Chet; Zhao, Guohua; Magnin, David R.; Augeri, David J.; Gungor, Timur; Rotella, David; Sun, Zhong; Liu, Yajun; Slusarchyk, William S.; Marcinkeviciene, Jovita; Robertson, James G.; Wang, Aiying; Robl, Jeffrey A.; Atwal, Karnail S.; Zahler, Robert L.; Parker, Rex A.; Kirby, Mark S.; Hamann, Lawrence G.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 23, 01.12.2007, p. 6476-6480.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors

AU - Simpkins, Ligaya M.

AU - Bolton, Scott

AU - Pi, Zulan

AU - Sutton, James C.

AU - Kwon, Chet

AU - Zhao, Guohua

AU - Magnin, David R.

AU - Augeri, David J.

AU - Gungor, Timur

AU - Rotella, David

AU - Sun, Zhong

AU - Liu, Yajun

AU - Slusarchyk, William S.

AU - Marcinkeviciene, Jovita

AU - Robertson, James G.

AU - Wang, Aiying

AU - Robl, Jeffrey A.

AU - Atwal, Karnail S.

AU - Zahler, Robert L.

AU - Parker, Rex A.

AU - Kirby, Mark S.

AU - Hamann, Lawrence G.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with β-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold.

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KW - DPP4

KW - Diabetes

KW - GLP-1

KW - Non-nitrile

KW - Serine protease

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JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

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ER -